Investigating ErbB receptor tyrosine kinases in cancer and modulation by membrane-bound serine proteases

The main research focus in the Chai laboratory is a novel “extracellular membrane-associated serine protease proteolytic activation and action network”, involving the glycosylphosphatidylinositol (GPI)-anchored prostasin (PRSS8), the type-II transmembrane hepsin (TMPRSS1) and matriptase (PRSS14), and the urokinase-type plasminogen activator (uPA) with its GPI-anchored plasma membrane receptor uPAR. This novel serine protease activation and action network has direct impacts on the cellular signals mediated by two major classes of membrane receptors, the receptor tyrosine kinases (RTKs) represented by the epidermal growth factor receptor (EGFR/ErbB1/Her-1) and the G-protein-coupled receptors (GPCRs) such as the protease-activated receptor 2 (PAR-2). Ultimately, this extracellular membrane-associated serine protease activation and action network is essential for maintaining epithelial homeostasis but is also implicated in the pathophysiology of many epithelial cancers. Currently we are investigating the proteolytic actions of these extracellular membrane-associated serine proteases on all members of the ErbB family RTKs using breast cancer cells as the study subject.